Our general goal is to understand the pathophysiology osteolytic response of bone to invading breast adenocarcinoma cells. Osteolysis primarily requires cancer-mediated dysregulation of cells from the osteoclasi lineage, but other cells types are also critically involved e.g. stromal cells, osteoblasts, and endothelial cells. We plan to identify some of the regulatory factors relevant to osteolysis which are produced by metastatic adenocarcinoma cells. The specific aim of this study is to analyze the expression of the ligand RANKL and its decoy receptor OPG by bone cells in response to breast carcinoma cells grown under different co-culture conditions, and to determine whether breast carcinoma cells also express RANKL or OPG or whether proteinases induced in bone or secreted by breast carcinoma cells inactivate RANKL or OPG.